title: Regional heterogeneity of substance P-induced endothelium-dependent contraction, relaxation, and -independent contraction in rabbit pulmonary arteries.
abstract: OBJECTIVE
  The present study examined whether substance P (SP)-induced endothelium-dependent TXA(2)-mediated contraction (EDC), nitric oxide (NO)-mediated relaxation (EDR), and endothelium-independent contraction (EIC) are different between the rabbit proximal and distal intrapulmonary arteries.
  
  
  METHODS
  The helically cut strips of isolated proximal and distal arteries were fixed vertically between hooks in organ bath, and changes in isometric tension were measured.
  
  
  RESULTS
  SP-induced EDC was greater in the distal than proximal arteries, and EDR was greater in the proximal than distal arteries. However, under the complete blockade of NK(2) receptors and NO production, SP (10(-9)-3x10(-7) M)-induced EDC did not differ between proximal and distal arteries. Under the complete blockade of NK(2) receptors and TXA(2) production, SP (3x10(-10)-3x10(-8) M)-induced EDR was greater in the proximal than distal arteries. Neither contraction induced by U-46619, a TXA(2) agonist, nor relaxation by sodium nitroprusside, an NO donor, was different between both portions of the arteries. Both ionomycin (10(-8) M)- and l-arginine (1 mM)-induced EDRs were also significantly greater in the proximal than distal arteries. Under the blockade of NK(1) receptors and NO and TXA(2) production, SP (10(-7) M)-induced EIC was greater in the distal than proximal arteries. In summary, the capacity for NO production is higher in the proximal than distal arteries, resulting in SP-induced higher EDR and lower EDC in the proximal arteries.
  
  
  CONCLUSIONS
  These regional differences in responses to SP may play important roles in maintaining the homogenous distribution of blood flow in the lung.
authors.affiliation: Pharmacology Division, RI Research Center, Kyoto University, Kyoto 606-8501, Japan. miike@kyoto-pharm.co.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miike
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shirahase
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kanda
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kunishiro
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000819:agonists / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D020030:Nitric Oxide Donors; D018041:Receptors, Neurokinin-2; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D013373:Substance P; D013928:Thromboxane A2